Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening
(2023) In Alzheimer's and Dementia 19(4). p.1393-1402- Abstract
Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ42/Aβ40 for amyloid positivity prescreening. Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ42/Aβ40 evaluated the actionability of plasma Aβ42/Aβ40, and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results: Elecsys plasma Aβ42/Aβ40... (More)
Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ42/Aβ40 for amyloid positivity prescreening. Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ42/Aβ40 evaluated the actionability of plasma Aβ42/Aβ40, and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results: Elecsys plasma Aβ42/Aβ40 could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in Aβ42 and/or Aβ40 cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. Discussion: Implementing plasma Aβ42/Aβ40 for routine clinical use may pose significant challenges, with misclassification risks. Highlights: Plasma Aβ42/Aβ40 ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma Aβ42/Aβ40 had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.
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- author
- Rabe, Christina ; Bittner, Tobias ; Jethwa, Alexander ; Suridjan, Ivonne ; Manuilova, Ekaterina ; Friesenhahn, Michel ; Stomrud, Erik LU ; Zetterberg, Henrik LU ; Blennow, Kaj LU and Hansson, Oskar LU
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, amyloid, biomarkers, blood biomarkers, prescreening
- in
- Alzheimer's and Dementia
- volume
- 19
- issue
- 4
- pages
- 1393 - 1402
- publisher
- Wiley
- external identifiers
-
- scopus:85139000666
- pmid:36150024
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.12801
- language
- English
- LU publication?
- yes
- id
- d04a1fa4-24c8-4f10-b40f-55c94971b79a
- date added to LUP
- 2022-12-22 09:44:01
- date last changed
- 2024-06-25 09:24:40
@article{d04a1fa4-24c8-4f10-b40f-55c94971b79a, abstract = {{<p>Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> for amyloid positivity prescreening. Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> evaluated the actionability of plasma Aβ<sub>42</sub>/Aβ<sub>40</sub>, and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results: Elecsys plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in Aβ<sub>42</sub> and/or Aβ<sub>40</sub> cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. Discussion: Implementing plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> for routine clinical use may pose significant challenges, with misclassification risks. Highlights: Plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma Aβ<sub>42</sub>/Aβ<sub>40</sub> had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.</p>}}, author = {{Rabe, Christina and Bittner, Tobias and Jethwa, Alexander and Suridjan, Ivonne and Manuilova, Ekaterina and Friesenhahn, Michel and Stomrud, Erik and Zetterberg, Henrik and Blennow, Kaj and Hansson, Oskar}}, issn = {{1552-5260}}, keywords = {{Alzheimer's disease; amyloid; biomarkers; blood biomarkers; prescreening}}, language = {{eng}}, number = {{4}}, pages = {{1393--1402}}, publisher = {{Wiley}}, series = {{Alzheimer's and Dementia}}, title = {{Clinical performance and robustness evaluation of plasma amyloid-β<sub>42/40</sub> prescreening}}, url = {{http://dx.doi.org/10.1002/alz.12801}}, doi = {{10.1002/alz.12801}}, volume = {{19}}, year = {{2023}}, }